The dynamic evolution of circulating tumor cells during glecirasib treatment predicts survival and resistance in gastrointestinal tumors with KRASG12C mutation.
Summary
This study investigated the dynamics of circulating tumor cells (CTCs) in 18 patients with advanced KRASG12C-mutated solid tumors treated with glecirasib, a KRASG12C inhibitor. Researchers observed an evolution in CTC subtypes (epithelial, mesenchymal, mixed) during treatment, particularly an increase in mixed CTCs at progression. Baseline CTC levels and their changes correlated with progression-free survival and overall survival. Furthermore, adding local radiotherapy for progressive lesions in patients with more than one CTC at progression significantly prolonged survival.
Analysis
Clinique: This phase I/II study highlights the potential of CTCs as prognostic and predictive biomarkers in KRASG12C solid tumor patients treated with glecirasib. High baseline CTC counts are associated with shorter progression-free survival, while low levels of certain CTC subtypes correlate with improved survival. The finding that local radiotherapy improves survival in patients with a high CTC burden at progression suggests a potential combinatorial therapeutic strategy, warranting further clinical trials to validate this approach. Clinical impact could be seen in 3-5 years. Biomol: The discovery of the dynamics of CTC subtypes (epithelial, mesenchymal, mixed) and their correlation with disease progression and resistance to glecirasib represents a significant translational advance. The increase in mixed CTCs at progression suggests a role for epithelial-mesenchymal transition in resistance mechanisms. The use of a microfluidics platform (CTC100, Cellomics) for CTC isolation demonstrates a robust technological approach for analyzing these blood-based biomarkers. These findings could lead to the development of companion diagnostic tests to guide treatment and resistance management.